The field of diagnostics is rapidly expanding. With increasing knowledge of diseases, more and more refined diagnostic tools are becoming available. These diagnostics typically use specific characteristics of a disease. These specific characteristics are, more often than not, genetic characteristics. These can be monitored on the protein level or on the nucleic acid level. Current trends are toward very precise diagnostics using specific genetic markers or antibodies or brute force methods using arrays of many different specific markets. These tests are very often designed to ever more finely discriminate between diseases and individuals. This increasing discrimination power often means that individuals are screened several times with increasingly refined diagnostic tests.
Methods of the present invention provide information at the top of this diagnostic cascade and are simple enough to incorporate in routine health screenings and check-ups. To this end, the invention provides a method for determining a health status of an individual comprising determining mitochondrion-bound nucleic acid in a sample of body fluid or feces of an individual. Body fluid and feces contain mitochondria. These mitochondria are probably ultimately destined to be destroyed. However, they are sufficiently intact to allow the determination of nucleic acid that is contained therein or associated therewith. Mitochondrion-bound nucleic acid is determined and the amount detected is indicative for the health status of the individual.
With “mitochondrion-bound nucleic acid” is, therefore, meant nucleic acid that is present in mitochondria or associated therewith. Mitochondrion-bound nucleic acid comprises at least one sequence of a nucleic acid that is normally present in mitochondria from the species of the individual that the sample is derived from. Other nucleic acid may be associated with (cell-free) mitochondria as produced in the present invention. However, such other nucleic acid, for instance, nucleic acid comprising a sequence that is normally found in the nucleus of a cell of the species that the individual belongs to, is not mitochondrion-bound nucleic acid as defined in the present invention.
Body fluid, such as lymph fluid, blood, urine, brain fluid or saliva also contains cells that also contain mitochondria. In the present invention, it is preferred that cell-free mitochondrion-bound nucleic acid is determined. “Cell-free” in this context means that mitochondria that are associated with cells, either internal to or linked thereto, are not considered.
Cell-free mitochondrion-bound nucleic acid can be determined in various ways. One way is to determine the amount of total mitochondrion-bound nucleic acid and the amount of cellular mitochondrion-bound nucleic acid in the sample and subtracting the amount of cellular mitochondrion-bound nucleic acid from the amount of total mitochondrion-bound nucleic acid. However, in samples that are rich in cells (such as blood), it is preferred that cellular mitochondria are essentially removed from the sample prior to determining cell-free mitochondrion-bound nucleic acid. Removal is typically done by utilizing the difference in density and/or size of the mitochondrion compared to intact cells. However, more specific means, such as antibody-based separation methods, are also possible.